Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT01104259|
Recruitment Status : Completed
First Posted : April 15, 2010
Last Update Posted : August 10, 2017
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor-negative Breast Cancer HER2-negative Breast Cancer Hereditary Breast/Ovarian Cancer - BRCA1 Hereditary Breast/Ovarian Cancer - BRCA2 Male Breast Cancer Progesterone Receptor-negative Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer Triple-negative Breast Cancer||Drug: veliparib Drug: cisplatin Drug: vinorelbine tartrate Other: laboratory biomarker analysis Other: pharmacological study||Phase 1|
I. To determine the maximum tolerated dose (MTD) of ABT-888 (veliparib) when administered daily for 14 days out of a 21 day cycle in combination with cisplatin and vinorelbine (vinorelbine ditartrate) in subjects with metastatic triple negative breast cancer (TNBC) and breast cancer (BRCA) mutation associated breast cancer.
I. Assess the pharmacokinetic profile of ABT-888 when combined with cisplatin and vinorelbine and the safety/tolerability profile of the combination.
II. Evaluate the level of poly ADP ribose polymerase (PARP) inhibition at each dose level to determine whether maximal PARP inhibition is achieved.
III. Identify the subgroup of triple negative breast cancer patients who will potentially derive the most benefits from PARP inhibition combined with platinum-based chemotherapy.
OUTLINE: This is a dose-escalation study of veliparib.
Patients receive veliparib orally (PO) twice daily (BID) on days 1-14 (days 0-13 of course 1 only). Patients also receive cisplatin intravenously (IV) over 1 hour on day 1 and vinorelbine ditartrate IV over 10-20 minutes on days 1 and 8. Treatment repeats every 21 days for 6-10 courses in the absence of disease progression or unacceptable toxicity. Treatment with veliparib alone may continue in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up to 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of ABT-888 in Combination With Cisplatin and Vinorelbine for Patients With Advanced Triple Negative Breast Cancer and/or BRCA-Mutation Associated Breast Cancer|
|Actual Study Start Date :||July 2010|
|Actual Primary Completion Date :||February 2015|
|Actual Study Completion Date :||April 2017|
U.S. FDA Resources
Experimental: Treatment (veliparib with cisplatin and vinorelbine tartrate)
Patients receive veliparib PO BID on days 1-14 (days 0-13 of course 1 only). Patients also receive cisplatin IV over 1 hour on day 1 and vinorelbine ditartrate IV over 10-20 minutes on days 1 and 8. Treatment repeats every 21 days for 6-10 courses in the absence of disease progression or unacceptable toxicity. Treatment with veliparib alone may continue in the absence of disease progression or unacceptable toxicity.
Other Name: ABT-888Drug: cisplatin
Other Names:Drug: vinorelbine tartrate
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
- MTD of veliparib, defined as the highest dose tested in which fewer than 33% of patients experienced dose-limiting toxicity attributable to the study regimen, when at least 6 patients were treated at that dose and were evaluable for toxicity [ Time Frame: Day 21 ]
- Toxicity profile, defined by the incidence of toxicity, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days post-treatment ]
- Pharmacokinetic (PK) parameters of veliparib in plasma and urine samples [ Time Frame: Baseline and day 1 of courses 1 and 4 ]The PK parameters determined will be: AUC0-t (the area under the concentration-time curve over a dosing interval), Cmax (maximal concentration), Tmax (time to maximal concentration), Vd (volume of distribution), CL/F (oral clearance for veliparib), CL (clearance for cisplatin), and t1/2 (elimination half-life). To improve understanding of systemic bioavailability, the amount of veliparib excreted in the urine for each collection interval will be calculated by the product of urinary drug concentration and urine volume.
- Pharmacokinetic (PK) parameters of cisplatin in plasma samples [ Time Frame: Baseline and day 1 of courses 1 and 4 ]The PK parameters determined will be: AUC0-t, Cmax, Tmax, Vd, CL/F, CL, and t1/2 .
- Pharmacodynamic parameters of PARP inhibition [ Time Frame: Baseline and day 1 of courses 1 and 4 ]Assessed by measuring changes in PAR levels in peripheral blood mononuclear cells and in tumor tissue (if available).
- Progression-free survival [ Time Frame: The number of days from the date the subject started study drug to the date the subject experiences an event of disease progression, or to the date of death if disease progression is not reached, assessed up to 30 days ]Estimated using Kaplan-Meier methodology and 95% confidence interval.
- Time to disease progression [ Time Frame: The number of days from the date the subject started study drug to the date of the subject's disease progression, assessed up to 30 days ]Estimated using Kaplan-Meier methodology and 95% confidence interval.
- Proportion of patients achieving a complete response (CR) or partial response (PR) (objective response rate) [ Time Frame: Up to 30 days ]Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 and estimated with 95% confidence interval.
- Duration of overall response [ Time Frame: The number of days from the day the criteria are met for CR or PR (whichever is recorded first) to the date that progressive disease is objectively documented, assessed up to 30 days ]Estimated using Kaplan-Meier Methodology.
- ECOG performance status [ Time Frame: Up to 30 days ]Descriptive statistics will be summarized for each assessment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01104259
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Jennifer Specht||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|